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S145 Week 24 Efficacy and Safety Data from PRISM3: A Randomized, Placebo-Controlled Trial Evaluating CP101, an Investigational Orally Administered Microbiome Therapeutic for the Prevention of Recurrent C. difficile Infection

2021· article· en· W3209098923 on OpenAlexaff
Jessica R. Allegretti, Colleen Kelly, Thomas Louie, Monika Fisher, Susy Hota, Bharat Misra, Nicholas W. Van Hise, Eugene F. Yen, Facg, John Pullman, Richard Nathan, Michael Silverman, Ian Davis, Sarah McGill, Sahil Khanna, Darrell S. Pardi, Robert Orenstein, Ari Grinspan, Najwa El‐Nachef, Colleen S. Kraft, Shrish Budree, Thomas J. Borody, Zain Kassam

Bibliographic record

VenueThe American Journal of Gastroenterology · 2021
Typearticle
Languageen
FieldMedicine
TopicClostridium difficile and Clostridium perfringens research
Canadian institutionsDalhousie UniversityUniversity Health NetworkUniversity of TorontoSt Joseph's Health CareWestern UniversityUniversity of Calgary
Fundersnot available
KeywordsMedicinePlaceboClinical endpointInternal medicineRandomized controlled trialClinical trialDosingAdverse effectClostridium difficileAntibioticsGuidelinePathology

Abstract

fetched live from OpenAlex

Introduction: Disruption of the microbiome is key to pathogenesis of recurrent Clostridioides difficile infection (CDI). Placebo-controlled trials assessing microbiome therapeutics have demonstrated efficacy in recurrent CDI; however, there is a paucity of data on response durability and long-term safety. CP101 is an investigational orally administered microbiome therapeutic designed to restore microbiome diversity and enable early intervention in the management of recurrent CDI. Given its complete consortia composition, CP101 is hypothesized to have a durable effect. Methods: We conducted a double-blind, randomized, placebo-controlled trial (PRISM3) enrolling adults who received standard-of-care antibiotics for recurrent CDI. Patients with first CDI recurrence at high-risk for further recurrence (≥65 years), or those with two or more recurrences were eligible. The qualifying CDI episode was diagnosed prior to study entry by guideline recommended testing (PCR-based or toxin EIA-based). Following CDI antibiotics, eligible participants were randomized 1:1 to receive one-time oral administration of CP101 or placebo without bowel preparation. The primary efficacy endpoint was sustained clinical cure, defined as an absence of CDI recurrence through Week 8 following dosing. Secondary endpoints of efficacy and safety were evaluated through Week 24. Results: 198 enrolled participants were analyzed with 28.8% of participants having one CDI recurrence prior to study entry and 61.1% of the qualifying CDI episodes diagnosed by PCR-based testing. Baseline characteristics were similar between CP101 (n=102) and placebo (n=96) arms. As previously reported, the CP101 arm demonstrated a statistically significant and clinically meaningful improvement in sustained clinical cure compared to the placebo arm through Week 8. On long-term assessment, CP101 demonstrated clinically meaningful durability and the proportion of participants with sustained clinical cure through Week 24 remained significantly higher in the CP101 arm compared to placebo (73.5% [75/102] vs 59.4% [57/96], P=0.0347) (Fig. 1a). Time-to-event analysis through Week 24 showed a statistically significant and durable benefit, favoring CP101 compared to placebo (P=0.018) (Fig. 1b). Through Week 24, adverse events were similar across both arms, and no treatment-related SAEs were reported with CP101. Conclusion: On long-term assessment, CP101 demonstrated durable efficacy for the prevention of recurrent CDI and a safety profile similar to placebo through Week 24.Figure 1.: a. CP101 demonstrated durable efficacy for the prevention of recurrent CDI in PRISM3. b. CP101 demonstrated a durable effect over time compared to placebo in PRISM3.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score0.050

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.005
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.004
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0150.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.101
GPT teacher head0.384
Teacher spread0.283 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2021
Admission routes1
Has abstractyes

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